Department of Neurobiology and Anatomy, The University of Texas Medical School, Houston, Texas 77225, United States. p.dash@uth.tmc.edu

Abstract

Recent studies have shown that sulforaphane, a naturally occurring compound that is found in cruciferous vegetables, offers cellular protection in several models of brain injury. When administered following traumatic brain injury (TBI), sulforaphane has been demonstrated to attenuate blood-brain barrier permeability and reduce cerebral edema. These beneficial effects of sulforaphane have been shown to involve induction of a group of cytoprotective, Nrf2-driven genes, whose protein products include free radical scavenging and detoxifying enzymes. However, the influence of sulforaphane on post-injury cognitive deficits has not been examined. In this study, we examined if sulforaphane, when administered following cortical impact injury, can improve the performance of rats tested in hippocampal- and prefrontal cortex-dependent tasks. Our results indicate that sulforaphane treatment improves performance in the Morris water maze task (as indicated by decreased latencies during learning and platform localization during a probe trial) and reduces working memory dysfunction (tested using the delayed match-to-place task). These behavioral improvements were only observed when the treatment was initiated 1h, but not 6h, post-injury. These studies support the use of sulforaphane in the treatment of TBI, and extend the previously observed protective effects to include enhanced cognition.

Performance in the Morris water maze task was tested 14 days after injury. Sulforaphane (5 mg/kg) or vehicle was administered by i.p. injection at either A) 6 hr, B) 6hr and 24hr, or C) 1hr and 24hr post-injury. ↓, time of injection. MWM: Morris water maze. DMTP: delayed match-to-place task. +, significant group main effect. *, p <0.05 between vehicle and sulforaphane groups.

Improved water maze performance is associated with enhanced measures of spatial localization

Twenty-four hours following the completion of training, rats were tested in a probe trial. A) Representative probe traces of swimming paths for a sulforaphane and a vehicle injected animal. The trace shows the path taken from the time of maze entry to the first crossing of the platform location. B) Quantification of time spent in each quadrant of the water maze during the probe trial. *, significant differences in dwell time. C) The latency to enter concentric circles (4X, 3X, 2X or 1X the diameter of the platform) centered on the platform (+, significant group main effect). D) Platform crossings during the probe trial. Data are represented as mean ± SEM. *, p <0.05 between vehicle and sulforaphane groups.

Schematic diagram showing the protocol of delayed match-to-place testing consisting of location (Loc) and match trials, separated by a 5 sec delay. Five pairs of location and match trials were performed, with the platform position in a novel site for each pair. Each pair of trials was separated by a 4 min inter-trial interval. B) Representative traces of a vehicle and a sulforaphane (Sul)-treated animal during the location and match trials. C) Summary data showing average latencies to the platform during the location and match trials. +, significant interaction between trial number and treatment groups; *, p<0.05 between location and match trials. Data are represented as mean ± SEM.